From Binding-Induced Dynamic Effects in SH3 Structures to Evolutionary Conserved Sectors.

Src Homology 3 domains are ubiquitous small interaction modules known to act as docking sites and regulatory elements in a wide range of proteins. Prior experimental NMR work on the SH3 domain of Src showed that ligand binding induces long-range dynamic changes consistent with an induced fit mechanism. The identification of the residues that participate in this mechanism produces a chart that allows for the exploration of the regulatory role of such domains in the activity of the encompassing protein.

Two-state dynamics of the SH3-SH2 tandem of Abl kinase and the allosteric role of the N-cap.

The regulation and localization of signaling enzymes is often mediated by accessory modular domains, which frequently function in tandems. The ability of these tandems to adopt multiple conformations is as important for proper regulation as the individual domain specificity. A paradigmatic example is Abl, a ubiquitous tyrosine kinase of significant pharmacological interest.

Interfacial water molecules in SH3 interactions: Getting the full picture on polyproline recognition by protein-protein interaction domains.

The recognition of proline-rich sequences by protein-protein interaction modules is essential for many cellular processes. Nonetheless, in spite of the wealth of structural and functional information collected over the last two decades, polyproline recognition is still not well understood. The patent inconsistency between the generally accepted description of SH3 interactions, based primarily on the stacking of hydrophobic surfaces, and their markedly exothermic character is a clear illustration of the higher complexity of these systems.